Is COL18A1 p.Ser830= (c.2490C>T) pathogenic?

COL18A1 p.Ser830= (c.2490C>T) is classified Conflicting classifications of pathogenicity in COL18A1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-19). Rare (popmax 0.247%, afr); Associated with Knobloch syndrome.

What condition is associated with COL18A1 p.Ser830= (c.2490C>T)?

COL18A1 p.Ser830= (c.2490C>T) is associated with Knobloch syndrome (ClinVar).

How common is COL18A1 p.Ser830= (c.2490C>T) in the general population?

COL18A1 p.Ser830= (c.2490C>T) is rare (popmax 0.247%, afr) (gnomAD).

COL18A1 p.Ser830=

c.2490C>T · rs377601838 · VCV899362

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.247%, afr)

Conditions

Knobloch syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP 0.13, phastCons 0.089
Overall
CADD	2.431	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.247% African / African-American · 185/74,986 alleles

Filtering AF 0.218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.206%

Overall 0.0138% 223/1,610,954 alleles · rare exomes 110/1,458,682 · genomes 113/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.247%	405
Remaining individualsnot grpmax-eligible	0.0225%	4,451
Admixed American	0.0217%	4,599
Middle Eastern	0.0165%	6,056
South Asian	0.0011%	90,520
European (non-Finnish)	0.000764%	130,957

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COL18A1
Protein: p.Ser830=
Coding: c.2490C>T
MANE Select: NM_001379500
dbSNP: rs377601838
Type: single nucleotide variant
Location: chr21:45495414 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.77 · 9 PDB
Residue 830: the 'triple-helical region 2 (col2)' region; the 'disordered' region

Full COL18A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Knobloch syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL18A1 c.3013+3A>C Likely pathogenic ★★ same condition
COL18A1 c.3809+2T>C Pathogenic ★★ same condition
COL18A1 p.Arg790Ter Pathogenic ★★ same condition
COL18A1 c.107-11479C>A Uncertain significance ★★ ⚠ same condition
COL18A1 c.107-12131C>T Uncertain significance ★★ ⚠ same condition
COL18A1 c.1311+5G>C Uncertain significance ★★ same condition
COL18A1 c.799-3C>G Uncertain significance ★★ same condition
COL18A1 p.Ala1156Thr Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/col18a1-p-ser830 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown